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Heroin took over. But was it a disease?

In this excerpt from The Biology of Desire, neuroscientist and former U of T professor Marc Lewis combines case studies and science to argue against the disease model of treating addiction.

Natalie used magic mushrooms, ecstasy, even LSD. These were "good" drugs. They didn’t hurt you, nobody got addicted to them, they weren’t very expensive, and you could still function the next day. Heroin was different. (Dreamstime)

By Marc LewisSpecial to the Star

Sun., Aug. 9, 2015

Natalie grew up in a town in the eastern United States and, like a lot of other kids of her age and circumstances, ended up going to a small liberal arts college in a nearby town. She describes herself as a pretty competent person, smart enough to get by. She could pick up the gist of a situation without obsessing over it; she knew how to stay out of trouble. She knew how to relax in social situations — or at least look relaxed. And by the time she got to college, at age 18, her peers found her generous, easygoing, fun to be with.

That’s how she described her younger self during our first couple of interviews. And it fit my impression of her, even now, in her mid-20s. It wasn’t difficult for Natalie to make friends, and she could pick and choose the people she wanted in her life. Natalie lived in a dorm for her first year of college, then moved to a shared apartment at the beginning of year two. She’d found a willing housemate in Grace, who liked being around Natalie, liked her quirkiness, her funny little hobbies like knitting and watercolours.

She and Natalie would sometimes spend an afternoon painting together. But Grace faded into the background when Natalie found a boyfriend: a mild-mannered, sweet-looking guy named Fred. She’d met him at the restaurant where she worked three days a week, serving the kids she sat beside in Introductory Philosophy and Twentieth-Century Literature.

She joked with him about how grandiose those students were, broadcasting their seasoned opinions about everything and everyone; then the two of them chuckled about their own grandiosity, putting everyone in their place. Fred was a pal, then suddenly a lover. That was new for Natalie, but it was also about time. Sex with Fred was friendly. And that was an achievement too — intimacy rather than subordination.

A couple of months after she and Fred got together, she brought home another friend, Steve — tall and lanky, a marijuana leaf tattooed on his forearm and a country-boy accent. There was something about Steve she found mysterious and attractive, but he was definitely not boyfriend material. Grace liked Fred well enough, but she wasn’t particularly thrilled with Steve. He seemed to bring out Natalie’s dark side, something vulnerable and spooky that didn’t match the rest of her. Something that seemed to break through the surface more and more as the months went by.

But Natalie was still a good kid. Everyone thought so. Which is why nobody — not Grace, Fred, or even Steve — could have imagined that Natalie would spend nine months in a maximum-security prison before she got close to graduation.

"The physical addiction was never foremost in my mind. It was far more the psychological," Natalie told Marc Lewis. (Spencer Platt/Getty Images)

Natalie had no particular moral compunctions about drugs, and she, Fred and Steve experimented, like many of their friends, with whatever was going around. Magic mushrooms, even LSD once in a while — these were tickets to an exotic Disney World that you could visit without much planning or expense. The trip started and ended in a mere eight hours, ideal for strolling through the park and watching the sunlight devolve into rainbow highlights, so beautiful they sometimes made you catch your breath.

And then there was ecstasy, great for dancing at one of the two local rock cafés … These were “good” drugs. They didn’t hurt you, nobody got addicted to them, they weren’t very expensive, and you could still function the next day — though perhaps not with utmost clarity.

Heroin was different. I found it hard at first to imagine how this darkest of drugs had insinuated itself into Natalie’s world. According to her recollections, the way was paved by a budding infatuation with prescription drugs, like the OxyContins Steve came up with. OxyContin, Percocet, Dilaudid — these are pharmaceutical opiates, designed to relieve pain. But Natalie and Fred found them to be just about the most pleasant high imaginable. They didn’t pitch you into a colourful fairyland, the way mushrooms and acid did. Instead they wrapped you in a stocking of inner peace, utter relaxation.

Not the kind of sedation you’d get from a tranquilizer, but something subtler and yet more potent. A feeling of well-being that didn’t result from suppressing everything, making you drowsy and dopey. Opiates relaxed you by abolishing the sensation of threat and letting your mind wander freely in the fanciful landscape left in its place.

Natalie hadn’t thought about it much, but a background hum of potential threat had been part of her world for years. It was hard to define, she told me, but it felt like a risk of failing one way or another — academically, maybe, or more likely socially. That was what mattered most, what had mattered since before high school, when she’d become a semi-regular victim of teasing about being “dumpy,” as she put it.

Nothing terrible, but hard to tolerate nevertheless — an ongoing threat that got under her skin, a corrosive anxiety about being rejected by classmates who seemed like friends but might mutate into persecutors by next week. And even now, as a sophomore with a job, a boyfriend, and reasonable grades, she could imagine losing what she’d managed to gain. It could still happen.

Some misty layer of anxiety was always floating just above the surface of things. Until opiates took it away.

So when Steve got a new batch of Oxys, which seemed to happen more and more often, Natalie felt a glow of anticipation. That’s when the synapses in her brain began a new wave of growth, forging a new set of connections. And when those synapses were activated, it felt to her like an approaching brightness, an arrow of hope. Fred liked the Oxys too, though she wasn’t quite sure why.

Natalie and Fred would purchase enough for a few days and enjoy it together after classes or after work. But opiates affect the body, not just above the neck but also below it, stilling the stomach and slowing the breath and pulse. So it started to feel uncomfortable to go without them after a few weeks. Something went missing not only from her mood but from her body’s familiar rhythms. We can call that a physical addiction, over and above Natalie’s budding psychological addiction. (Though, of course, everything is physical. The brain is part of the body too.)

The other problem was tolerance, another sign of so-called physical addiction. By the time spring came around, Natalie and Fred had to take three or four 20-milligram pills to feel high. And that got expensive, even when they crushed up the pills and snorted them. Nobody was making enough money to keep that going and still pay the rent on time.

Heroin was a lot cheaper, and Steve looked pretty cocky when he tossed a couple of $20 bags on the table one March afternoon.

Fred and Natalie smoked it in a hastily renovated hash pipe, following Steve’s example. But snorting it worked just as well, and that became their preferred MO in the following weeks. The high was actually quite a bit more intense than what they got from Oxys, but OK, bonus prize. An almost shocking river of peace would wash over her just a few moments after getting the heroin into her lungs or her mucous membranes. And there was something better than before to look forward to next time around. Synapses kept sprouting; neurons kept connecting …

Still, heroin didn’t dominate Natalie’s life. “I had a lot of other things to think about,” she told me, including her grades, her job, the balancing act she had to maintain with her parents on weekends and holidays — all the more difficult now that her stepdad’s tantrums erupted so frequently. Heroin provided a welcome diversion, a reward at the end of a tough day, a psychic picnic table that she, Fred, Steve, and a few other friends could return to again and again. But she didn’t need it. Not yet.

Then she tried shooting it. She watched Steve’s girlfriend enact this grisly routine and was instantly intrigued. She pulled the woman aside and asked her to show her how to do it. And Natalie, in her usual thorough and responsible manner, memorized every detail of that intricate ritual. Pouring the right amount of brown powder into the spoon, adding water, holding the spoon steadily over the front burner of the stove until it bubbled for a few seconds. The little cotton ball that was necessary to filter the solution. The tourniquet. The bulging of the vein on the inside of her arm. It all had to be undertaken calmly and cleanly, nothing spilled, nothing spoiled. Until the needle penetrated the vein and she would feel, at that second, that there was an open passage for this exotic suitor, this ambassador from Afghanistan or wherever it was, to enter her body, her heart, her brain.

Then there was nothing more to worry about, from the moment the needle pierced the vein, even before the drug transformed the chemistry of her nervous system. That wash of peace started with the knowledge that this was a sure thing, no longer a maybe. This was what she’d been looking for, perhaps for a very long time.

"It all had to be undertaken calmly and cleanly, nothing spilled, nothing spoiled," writes Marc Lewis in The Biology of Desire. "Until the needle penetrated the vein and she would feel, at that second, that there was an open passage for this exotic suitor, this ambassador from Afghanistan or wherever it was, to enter her body, her heart, her brain." (CHERYL SENTER/New York Times)

For Natalie, it wasn’t drugs in general, or opiates, or even heroin that changed her life. It was the practice of shooting up. First came the feeling of being overwhelmed, as if by a breaking wave, a half-hour of chemical aftershock. That was cool. And so was the way the parts came together to make a whole, all those details converging into something unique. “That whole ritual thing … I loved it,” she told me. “I would sometimes shoot up other people, because I was just better at it than others, and I enjoyed doing it for them.”

It seems Natalie was immersing herself in a dark liturgy. The skin and the steel, the bluish tint of the vein. The spoon and the flame, that moment of bubbling alchemy that marked the entrance into another dimension. And when the needle penetrated her own body, the feeling of the drug itself. The taste of it from inside. The click of shackles released all over her nervous system, reaching back to smooth every jagged memory, and forward, a guarantee of the hours to come, a guardian against harsh thoughts and images, the settling in of a consciousness infused with peace.

This harmony of sensations took up residence in Natalie’s mind as networks of synapses converged in her brain. And from that headquarters a heightened urgency began to rule. It took less than a month from the time she started injecting heroin until her days became sloped in a singular direction, each afternoon a curled surface that would wrap into the shape of a funnel, a downward slanting tube that must empty into the reservoir of the moment. That moment — the moment of shooting up. Inevitable, from the first lurching rotation of her mind’s eye to a point in time still hours away.

She’d be at the restaurant, working her shift, actually enjoying the summer sun streaming through the plate-glass windows, when suddenly it would strike. The thought, the image. It might be triggered by smoke rising from the cigarette of someone standing just outside the entrance.

Or by the peculiar flattening of a spoon sitting next to the dirty plate on a nearby table, calling to mind the misshapen spoon of the dope-shooter, bent so that the bowl remained horizontal when the spoon lay at rest. Or by the vibration of her cellphone, acknowledging a call from Fred, who might already have been in touch with Steve. Who might already have enough for all of them. For tonight.

Or by the gurgle of her stomach, which wasn’t working very well these days. Or by the sight of her own arm. With her sleeves rolled down, no one could tell. (Though everyone seemed to know that Natalie was living on a different planet.) But when she rolled up her sleeves to wash, she’d often catch sight of the dark penumbra of a bruise centred at the seam inside her elbow.

Whatever the trigger, the ride each time was a replay of her previous rides, that sensation of being catapulted from wish to deed.

First came the sudden tension in her stomach and chest, a lurching sensation of something imminent, a challenge or threat or golden opportunity, depending on how she played her hand. For a second or two the feeling had no colour, no content, and then it morphed into craving. She could not stop thinking about it from that moment onward, she recalls.

It invaded her reverie, her every thought, while she went about the practised motions of her work. She checked her phone every five minutes. She was sure that Steve would still be at home. It wasn’t past 1 yet. She’d send him a text message as soon as she got to the kitchen. But what if he’d already scored? He might be on his way back now. In Natalie’s words, “If he got stalled in traffic, it would be excruciating … I would literally stare at the phone, willing it to ring.” And when he did get back, would he have enough for all of them? What if he only had enough left for himself? Then she’d have to plead with him.

This kind of internal dialogue came out clearly in my interviews with Natalie. After some probing on my part, she remembered her thoughts as well as her deeds. She would rehearse the next phone call: C’mon, Steve. I’ll go with you if you want. I don’t mind. I’m off work at 5. And she would imagine the bleakness of failure: He likes my company. But what if he’s going away for the weekend?

S---, we should have saved enough. We put aside one bag, but that’s not nearly enough for both of us. Well, f--- Fred in that case. He’s always relying on me to take care of this. But what if he’s already called Steve? What if he forgot that I’m going home Friday night? I need to get enough for the weekend; otherwise it’s going to be totally awful to be with Mom and S---head.

It was impossible to ignore the moment inscribed in the future of this day, the moment when the drug would be in her grasp. Until then, the pit in her stomach — anticipation mixed with desire mixed with dreadful anxiety — would not lessen. It would not soften. Not until she knew for sure. And even then, something could always go wrong.

By May, Natalie was not yet so physically addicted that she couldn’t get through a day without heroin. But she was on her way.

Here’s how she describes her worries: “I knew I might be mildly uncomfortable tomorrow morning, and sure, it would get worse by evening. Two days without — hard to know.” She hadn’t gone two days without for weeks now. “It would probably feel like s---.” And yet she didn’t think about her addiction as physical. In her words:

“The physical addiction was never foremost in my mind. It was far more the psychological. I was getting obsessed with it. If we didn’t get it on a particular day, we would be up really early or up late that night, waiting for the phone to ring … ”

Cognitive neuroscientist Marc Lewis, himself a former addict, explains the changes drugs can produce in the brain — particularly in the accumbens, which has power to control attention, perception, feeling and action.

There are parts of the brain wrapped deeply within the cortical layers that we share with animals going all the way back to fish. These structures include a large and highly complicated crescent of tissue that sort of curls around the very centre of the brain. It’s called the striatum and it’s the main character — the villain — when it comes to addiction. The striatum evolved to select actions that lead to the achievement of goals. In fact, there’s not much point to actions that don’t lead to goals, so the striatum evolved for the express purpose of connecting actions with goals.

The striatum gets a goal on its radar and then sends an action “script” to other parts of the brain (like the motor cortex) to execute, to move the muscles in such a way as to get whatever it is you’re after: tapping the keys on your phone, reaching for your wallet, mouthing the words that will get the right response.

But the only way to get an animal to act is to motivate it (unless that action is directly programmed, like the flinching of a worm when you touch it, or the bounce of your leg when your knee gets a tap). Emotion, motivation — these were evolutionary experiments that started around the time mammals first got up off their bellies.

If mammals were going to learn from their experiences — unlike their cold-blooded forebears — they would need a more flexible operating system than the fixed action patterns responsible for the flinching of the worm and the darting of the frog’s tongue. So the part of the brain preserved deep within the cortex — the action brain, the striatum — also became the brain’s motivational centre. And it took charge of the one emotion that gets us to pursue our goals, often relentlessly: the emotion of desire.

As the brain’s action control headquarters, the striatum has the capacity to produce feelings of attraction and engagement, so crucial for forward-aimed action. But it also gauges the likelihood of meeting that goal, and once that goal is reached, it signals how rewarding (or disappointing) the goal was, compared to expectations.

So its job specs include producing the motivation to pursue something, determining how hard you have to try to get that thing, and feeling good (or not so good) about the goal once it is reached.

The striatum learns from experience. It adjusts its wiring according to what felt good in the past and how hard it was to achieve that feeling. Thus it translates past pleasures into present desires. When Natalie felt that wash of craving for a shot of heroin, imagining how good it was going to feel, working out what she had to do to get it, her striatum was buzzing.

The synaptic networks in her striatum included in the “heroin” pattern (flashing all over her brain) were alive with neuronal transmissions — firing rates well into the red zone, marked “urgent.” At the same time, her other goals, like pleasing her boss at the restaurant, getting on better with Grace, and calling her mom, all faded, became insubstantial. The networks that supported those goals dimmed and then turned dark. As with other brain networks, “what fires together wires together,” and what doesn’t fire together — with the rest of the team — gets left on the sidelines. Those synapses literally lose efficiency and may eventually disappear altogether.

The nucleus accumbens (or just “accumbens” for short) is one of the most ventral (lower) regions of the striatum. It is tucked deep down in the forebrain, underlying the cortex and limbic system, and it sends its outputs to many other brain parts. In an MRI scan, it shows up as a pair of spots, one in the left brain and one in the right (though it’s referred to in the singular: the accumbens). But those spots do a lot of work.

The accumbens is a dugout of ancient tissue, and it hums like an engine buried under the moving parts it controls — the other brain regions. The accumbens is the brain part you hear about most when it comes to addiction. It embodies the “hot” end of the striatum, the end with the most connections to other regions that give rise to emotions, expectancies, and actions.

To get you to your goal, the accumbens organizes neural activity, not only in the frontal cortex, where meaning is manufactured and expectancies formed, not only in the back of the cortex, where images and memories come alive, but also in the amygdala, which triggers emotional responses, in the brain stem centres that provide the pulp of emotional feeling, and in the premotor and motor cortex, where actions are choreographed and executed. Most of these connections go in both directions. The accumbens gets input from these regions.

That’s how images — needles and powder and the vein in her arm — could influence Natalie’s intentions and goals, her scripted pleas to Steve. But it also sends output to these regions, including the amygdala, which pulls all sorts of emotions into the mix, and the lower brain parts that could activate sweat glands and wake the butterflies in her stomach. The power of the accumbens to control attention, perception, feeling, and action is immense, and it uses that power to override the ragtag crowd of alternative goals, so that just one goal is left, now glowing with immediacy, pounding with importance. That’s where we’re going. That’s what we’re going to do.

The accumbens is often considered the brain region where desire is ignited. And most experts agree that intense desire, or craving, is the dark horse of addiction. But the accumbens needs fuel to jack up the firing rates of its neurons. And that fuel is dopamine, a neurochemical pumped up from the centre of the brain — the midbrain — located one floor down and a bit further back. Craving intensifies when the midbrain sends dopamine up to the accumbens. The more dopamine, the more the accumbens is activated, and the more we experience craving. I just really want it, and I want it right now! I know it’s going to feel good, or at least a whole lot better than how I feel without it. And nothing else matters.

Researchers used to talk about this machinery as the “pleasure circuit” — but it turns out that our intense pursuit of goals, like sex, heroin, and chocolate cheesecake, has a lot more to do with desire than with pleasure. Wanting something is not the same as liking something, and most of the accumbens is devoted to wanting. Pleasure is a pastry puff, a dessert, a flash in the pan. Desire is what gets us moving, whether that means calling your dealer, driving to the liquor store, or stealing 20 bucks from your aunt’s purse. Dopamine — at least where it’s absorbed in the striatum — is the fuel of desire, not fun.

A couple of researchers, Kent Berridge and Terry Robinson at the University of Michigan, provided two major upgrades to the neuroscience of addiction. The first was a map of the brain geography of wanting versus liking. What they found is that most of the striatum is in the business of wanting, and only a small area produces the sensation of liking. It seems that evolution devoted a lot more real estate to desire than to the end state — pleasure or relief — it sometimes achieves. Their second contribution was a formula for the growth of desire for specific goals with the rise of addiction, a formula that describes how drugs (and sex, and food, and other attractive things) end up triggering impulsive behaviour. Their work was mostly done with rats and mice, but our brains aren’t much different when it comes to the accumbens. The more their rodents were exposed to cues that predicted getting addictive drugs, or even sugar, the more those cues commandeered the accumbens.

The cue, the stimulus, whether it was a green light or a horizontal stripe, became increasingly likely to direct the animal’s attention and behaviour toward the reward. Berridge and Robinson called this process incentive sensitization. And the mechanism responsible was simply the tide of dopamine coursing up from the midbrain to the accumbens. Somewhere between the visual cortex (where the cue was registered as input) and the accumbens (in charge of output), experience altered the wiring, and the cue became the hand that cranked the dopamine pump. In fact, even secondary cues associated with drug-related cues took on that eerie potency. So you could have one cue predicting another cue that predicted getting high, and then the first cue in line — for example, the buzzing of Natalie’s cellphone — would start the ball rolling, start the dopamine flowing.

That was Natalie’s situation within a month of her unfortunate experiment injecting heroin. She couldn’t help the avalanche of excitement, desire, and anxiety triggered by that first hint of drugs on the horizon. This didn’t mean she was fated to go and get more heroin. Her actions were not bound and determined by the changes taking place in her brain. But her feelings and thoughts were changing in step. More and more often there came an unrelenting cascade of craving and a narrowing of attention — two streams converging into one — as long as the link between cue and outcome lit up the synaptic networks in her striatum like strings of Christmas bulbs.

And, of course, every time those bulbs lit up, it got harder to find the off switch. Every time she introduced a new stimulus to the “heroin” club, like a ringtone for the phone at Steve’s parents’ house, it got initiated into the fraternity and acquired power over the dopamine pump. Now there were more roads leading to Rome. Now there were more “heroin” synapses linked with each other, so firing rates would climb more quickly, more easily, more predictably, from a greater range of starting points.

That’s how Natalie developed a serious habit. It’s not that she was forced to act on cue — but it became harder and harder to resist the temptation.

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